Patients with cystic fibrosis (CF) have significant morbidity and mortality due to airway infections. These infections are related to the deficiency of mucociliary clearance due to thick dehydrated secretions. Thus, considerable effort is spent managing airway infections. This includes therapies to improve mucus clearance and antibiotic treatments that target important pathogens. Understanding the source of airway microbiota, increased risk of infection, and exacerbation is critical to improve management of airway infection. A large proportion of CF patients are also treated with anti-acid medications. These medications decrease symptoms associated with gastroesophageal reflux disease (GERD), and improve the efficacy of enzyme replacement therapies. Critical for this proposal is the fact that aspiration may represent a potential route for airway infection from microorganisms in the upper gastrointestinal (GI) tract, and anti-acid treatments shift the GI microbiota. In preliminary studies we have identified a strong alteration of the esophageal microbiota in subjects using acid blocking medications. Thus, these treatments may have a significant effect on the bacterial communities present in the upper GI tract and may play a role in infection and exacerbation in CF. Traditionally, access to the upper GI tract has required endoscopy to acquire biopsy tissue, which is an invasive procedure and not routinely performed in CF. To circumvent the invasive sampling required for study of the esophagus we have recently shown that a minimally invasive test, the esophageal string test (EST), is capable of sampling the upper GI tract, and has performance comparable to biopsy for a number of measurements including assessment of the esophageal microbiota.